Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article, we describe a 46-year-old man with severe high-density lipoprotein (HDL) deficiency and his kindred. In the proband, HDL cholesterol and apolipoprotein (apo) A-I levels were 5 and 4.5 mg/dL, respectively. Xanthomata, xanthelasma, arcus corneae, and hepatosplenomegaly were not present. The proband had coronary artery disease, but it was impossible to state whether the HDL deficiency cosegregated with premature coronary artery disease in this kindred. Pedigree analysis was suggestive of a codominant familial disease. Polymerase chain reaction amplification of the apoA-I gene of the proband, followed by subcloning and sequencing, did not reveal any mutation in either the coding regions or intron-exon junctions. A kinetic study using deuterated leucine to endogenously label apoA-I was performed to elucidate the metabolic basis of the apoA-I deficiency. We demonstrated marked hypercatabolism of apoA-I in the proband, with a fractional catabolic rate more than 10 times faster than normal; the plasma residence time of apoA-I in the proband was only 0.38 day compared with 4.10 days in a control subject. The apoA-I production rate was also substantially decreased in the proband. The association of a normal apoA-I gene sequence with marked hypercatabolism of apoA-I is similar to that described in Tangier disease. However, except for the presence of mild, diffuse, corneal deposits, this patient had no evidence of the reticuloendothelial cholesterol deposition characteristic of Tangier disease. This study establishes that a form of severe hypoalphalipoproteinemia distinct from Tangier disease can be caused by marked hypercatabolism of a normal A-I apolipoprotein.
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PMID:Familial HDL deficiency due to marked hypercatabolism of normal apoA-I. 836 14

Cholesteryl Ester Storage Disease (CESD) is a rare recessive disorder due to mutations in LIPA gene encoding the lysosomal acidic lipase (LAL). CESD patients have liver disease associated with mixed hyperlipidemia and low plasma levels of high-density lipoproteins (HDL). The aim of this study was the molecular characterization of three patients with CESD. LAL activity was measured in blood leukocytes. In two patients (twin sisters) the clinical diagnosis of CESD was made at 9 years of age, following the fortuitous discovery of elevated serum liver enzymes in apparently healthy children. They had mixed hyperlipidemia, hepatosplenomegaly, reduced LAL activity (approximately 5% of control) and heteroalleic mutations in LIPA gene coding sequence: (i) the common c.894 G>A mutation and (ii) a novel nonsense mutation c.652 C>T (p.R218X). The other patient was an 80 year-old female who for several years had been treated with simvastatin because of severe hyperlipidemia associated with low plasma HDL. In this patient the sequence of major candidate genes for monogenic hypercholesterolemia and hypoalphalipoproteinemia was negative. She was found to be a compound heterozygote for two LIPA gene mutations resulting in 5% LAL activity: (i) c.894 G>A and (ii) a novel complex insertion/deletion leading to a premature termination codon at position 82. These findings suggest that, in view of the variable severity of its phenotypic expression, CESD may sometimes be difficult to diagnose, but it should be considered in patients with severe type IIb hyperlipidemia associated with low HDL, mildly elevated serum liver enzymes and hepatomegaly.
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PMID:Cholesteryl Ester Storage Disease (CESD) due to novel mutations in the LIPA gene. 1930 43